Merck report: $358m in Gardasil sales for Q2; $1 billion total for vaccines

While we don't typically highlight corporate earnings reports or similar news, the quarterly report released Monday by Merck for April-June 2007 provides some new information about the growing market for vaccines, and, in particular, Gardasil. Here's coverage from yesterday's New York Times, "Another Quarter of Strong Results by Merck," and a similar story from Reuters.

Since this news comes directly from the company, the Merck press release is particularly useful. Here's part of what it says about vaccines:

"Total vaccine sales, as recorded by Merck, were $1.0 billion for the quarter, compared to $349 million in the second quarter of 2006. The growth in vaccine sales was led by the performance of GARDASIL along with strong contributions from ROTATEQ and other pediatric vaccines. Vaccines in most major European markets are sold through the Company’s joint venture, Sanofi Pasteur MSD, and the results from its interest in the joint venture are recorded in equity income from affiliates.

Total sales as recorded by Merck for GARDASIL, the Company's cervical cancer vaccine, were $358 million for the second quarter. As of the second quarter, GARDASIL has been approved in 80 countries, many under fast-track or expedited review; and launched in 59 of those countries. The vaccine remains under review in approximately 40 other countries.

ROTATEQ, Merck's vaccine to help protect children against rotavirus gastroenteritis, achieved worldwide sales, as recorded by Merck, of $119 million for the quarter. As of the second quarter, ROTATEQ has been approved in 61 countries and it has launched in 22 of those countries."

The release goes on to note sales figures for Proquad ($89 million), Varivax ($147 million), and Zostavax ($47 million).

A companion document released by Merck breaks down sales between the U.S. market and internationally. Nearly 80% of Gardasil sales were in the U.S. ($286 million), as were an amazing 96% of RotaTeq sales ($114 million). There's little doubt from these data that the U.S. is leading the way in the uptake of these two fairly new vaccines, despite the far greater need for cervical cancer and rotavirus prevention internationally.

Overall, $1 billion in vaccine sales for a single company in a three-month period is perhaps the best evidence to date of the potential profitability of vaccines to an extent not previously seen. As for Gardasil, it is difficult to work backwards from the sales figures given ($358m) to ascertain the number of doses sold during the April-June period, since governments and insurance companies pay less than the well-known $120/dose 'sticker price'. This CDC price list shows a cost of $96.75/dose for Gardasil as part of the Vaccines for Children program. Using those figures as endpoints, a very rough estimate would suggest 3-4 million doses were sold, or enough doses to fully vaccinate slightly more than 1 million girls.

Given the size of the population for whom vaccination is recommended (all females 11-26), the potential growth of the Gardasil market is staggering, perhaps explaining, in part, the company's apparent enthusiasm to promote its vaccine in advance of the arrival of GSK's Cervarix.

Gardasil: CDC response on safety/efficacy; survey on parental support for mandates

The weekly news update from the Immunization Action Coalition alerted us to this CDC Q&A released last week titled "CDC Questions and Answers Concerning the Safety and Efficacy of Gardasil." The three-page document outlines the current status regarding safety monitoring, known safety concerns, the potential need for boosters, and the ongoing necessity of Pap screening.

It seems likely that the fact sheet was this breathless press release from JudicialWatch.org asserting (based on VAERS reports) that "three deaths were related to the vaccine." The CDC fact sheet clearly explains how and why this statement is a misinterpretation of VAERS data, reaching conclusions that are no possible from that information alone. Not surprisingly, a search of Google News suggests that the press release garnered virtually no attention from the print media. While safety concerns linked to Gardasil could still surface, there's no evidence at present to suggest such a connection.

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One other item related to Gardasil: The headline from a survey released by a group at the University of Michigan C.S. Mott Children's Hospital reads: "Majority of U.S. Parents Not in Favor of State HPV Vaccine Mandates." The report is available here, and here is coverage from CBS News and the Washington Times.

However, the headline -- while likely shrewdly written to generate the media coverage sampled above -- is very misleading. The report's own data (Table 1 in the report) lists 26% of parents disagreeing with an HPV mandate, 44% of parents agreeing, and a very significant 30% as 'neutral.'

Therefore, the same data could also carry the headline, "76% of parents not opposed to HPV mandate," which would actually more accurately capture the large percentage of respondents with no opinion for or against a mandate.

More Benefits of Gardasil?

With GSK's HPV vaccine -- Cervarix -- about to enter the final stages of FDA review prior to its all but certain licensure in the coming months, the marketing battle between GSK and Merck is about to begin in earnest.

One precursor of what's to come has been the occasional announcements and published papers noting protection against additional HPV strains beyond those specifically included in the vaccine. We've linked to many of those items previously.

Another sign is this headline: "Gardasil Guards Against Vaginal, Vulval Cancers: Researchers found cervical cancer vaccine reduced risk of lesions by 49%". The story is based on a paper in the latest issue of The Lancet by Joura and colleagues (abstract available here with free registration).

HPV Roundup -- CQ Report, Texas Aftermath, N.H. Success, and More

Another look at recent news and perspectives on Gardasil and HPV vaccine policy appearing in print or online...

• The latest issue of CQ Researcher -- the issue-focused publication affiliated with Congressional Quarterly -- looks exclusively at HPV vaccines and the debate over mandates. The 24-page report is well researched, extensively cited, and offers an incredible range of information as to the scientific, political, public health, and economic considerations in play. It might be the single best source for non-scientists looking to understand 'what all the fuss is about.' Sadly, access requires a subscription to www.cqresearcher.com, but it's likely that readers with university affiliations can access it through their libraries.

• This story in the New Scientist -- US Conservatives Block Cancer Vaccine for Girls -- updates the US state mandate landscape, particularly this month's Texas law effectively overriding Gov. Rick Perry's executive order in February. (More on the Texas legislation can be found here and here. Also, here is the text of Gov. Perry's remarks upon the bill's passage with veto-proof majorities.)

• A major contrast to the Texas saga is what's been happening with Gardasil in New Hampshire, as described in this story from the New York Times: "In New Hampshire, Soft Sell Eases Vaccine Fears." Instead of mandates, the state's practice of voluntary, free vaccination has led to a surge in demand for Gardasil, the story explains.

• We're just about exhausted with op-eds on HPV mandates. At this point, all one hears are the same arguments (for or against) over and over. Here's one that does attempt to say something new, courtesy of The Hastings Center's "Bioethics Forum": In "Choosing Paternalism?", Karen Maschke explores lessons from the U.S. Gardasil experience thus far that might be useful when considering the vaccine's implementation in the developing world.

• Earlier this month, this story in the Washington Post -- "Who Gets Stuck? Doctors, Patients Want Insurers to Pay More for Vaccines" -- looks at some of the reimbursement issues being raised by physicians, particularly the (small) amounts provided for vaccine-related costs beyond the price of the dose itself.

HPV mandates and more in JAMA and NEJM

There is a lot of discussion on HPV vaccination and mandates in recent issues of the New England Journal of Medicine and the Journal of the American Medical Association.

In the May 2 JAMA, Lawrence Gostin -- a professor of health law at Georgetown -- and Catherine DeAngelis -- the editor of JAMA -- wrote an editorial titled "Mandatory HPV Vaccination: Public Health vs Private Wealth." Gostin and DeAngelis reject mandates for HPV at this time, referring to any use of state mandates as "a last resort." Specifically, they point to questions regarding cost/payment, long-term safety, injury compensation, and the fact that HPV is not "a highly infectious airborne disease" to support their argument against mandates.

The latest NEJM includes seven pieces on HPV vaccines, including two commentaries, two reports, two editorials, and a letter. All are available for free here. Of note is the commentary by Alta Charo -- professor of law and bioethics at the University of Wisconsin -- titled "Politics, Parents, and Prophylaxis -- Mandating HPV Vaccination in the United States." Charo argues in favor of state mandates, pointing to the easy-to-secure exemptions available in every state in which a mandate has been explored. With essentially any parent objecting the vaccine having the ability to receive such an exemption, the overall merits of a state mandate greatly outweigh the slight inconvenience the exemption process imposes on parents seeking it, she suggests.

Also of interest is "Introducting HPV Vaccine in Developing Countries -- Key Challenges and Issues" by Agosti and Goldie. The authors point to availability, access, and cost concerns related to the international implementation of HPV vaccination programs.

New Mexico HPV bill vetoed

Following up on an earlier post, New Mexico Gov. Bill Richardson vetoed a bill earlier this month that would have added a school entry requirement for HPV vaccination among all sixth grade girls. The decision was a reversal from his earlier public comments, from which his signature seemed all but certain. Here's the AP story from the Santa Fe New Mexican.

Gardasil: Recommendations published, views on industry role, male vaccination, N.M. mandate, and more

Some updates from the past 10 days or so on recent news about Gardasil and the ongoing discussions about mandates...

• Last Monday, the official ACIP recommendations on Gardasil were published online in MMWR. These are essentially the same recommendations that were announced in June 2006 (which we first wrote about here) -- there is an increasingly longer lag between such announcements and publication in MMWR. One important consequence of publication is that it typically pressures insurance companies who have not yet agreed to cover the cost of the vaccine to do so.

• A story in today's Detroit Free Press asks, "Why aren't more girls getting HPV vaccine?" The story relies more on anecdotal reports than any real data, however. The two million doses of Gardasil shipped in the 9 months since licensure is a not-insignificant number, particularly considering the delays in insurance coverage in many cases. Nevertheless, it may be a question worth asking. This AP story may be relevant to the discussion, examining continued public ignorance about HPV, despite the attention it's received in the past year.
  

• An interesting (and provocative) opinion from Adrian Fugh-Berman on "Bioethics Forum" (the blog of the Hastings Center, the bioethics think-tank) -- "Cervical Cancer Vaccines and Industry Influence". Fugh-Berman's conclusion: "Cervical cancer is uncommon in the United States. This is not an emergency; this is not SARS. Listen only to public health people without conflicts of interest. There’s time for a discussion – but ban industry from the room in which any decisions on public health are made." Worth reading, regardless of one's own opinion on the topic.
  

• Following up on our colleague James Colgrove's perspective on HPV mandates in NEJM last fall (which we noted then), several letters to the editor were published earlier this month in response. One letter highlights the potential value of vaccinating males, and another takes issue with the use of the word "compulsory" to describe vaccination requirements that allow for informed refusal. This point goes to the increasing use of the term "opt-out requirement" when discussing what have traditional been known as state mandates.

• Speaking of vaccinating males, yesterday's Los Angeles Times took a closer look at some of the unique issues regarding HPV infection in men and the potential value of vaccination.
  

• New Mexico appears to be the next state on the verge of an HPV school-entry requirement. Here's a story from last week about the passage of a bill in its state legislature. As best as we can tell, the bill is still awaiting Gov. Bill Richardson's signature, which could happen at any time. Many other states -- too many to count -- have bills at some stage of the legislative process.

• The Powerpoint slides from last month's ACIP meeting were recently posted here. Updated Gardasil efficacy data from Merck's Eliav Barr are available there, as is a general overview of the American HPV vaccine landscape by CDC's Lauri Markowitz. It's very interesting for those looking for somewhat less-filtered information than what appears in the popular media.

Gardasil round-up: Merck lobbying, ACIP chair comments, Virginia mandate, and more

There continues to be a steady trickle of news about Gardasil, largely centered on the ongoing debate regarding possible state mandates. Rather than attempt to keep up with each day's new op-eds, news stories, and the rest, we've decided to combine several of the most interesting items from the past 10-14 days into a single post. With that, here are some recent items making headlines:

• Perhaps the biggest news from the past few weeks was Merck's decision to stop participating in lobbying efforts for state mandates. Here's one account of the story from late February, courtesy of Reuters. It quotes Merck's Richard Haupt calling the company's activities a "potential distraction." Few would disagree with this assessment, and it is surprising, given the company's extensive and seemingly well orchestrated marketing and education efforts, that it would commit so significant a public relations blunder.

• Since that announcement, there has been no shortage of stories and op-eds more or less making the same point, namely, that the Texas political controversy and Merck's lobbying efforts have obscured the scientific and medical aspects of the vaccine and its potential benefits. That's the thesis of this New York Times editorial, "A Necessary Vaccine," (subscription required) which generated a number of letters in response. Also: a story in today's Times titled "A Vital Discussion, Clouded."

• Sunday's Washington Post also looked at these issues ("Parents Question HPV Vaccine: Push to Mandate Shots Rapidly Creates Backlash") Quoted in this story is ACIP chair Dr. Jon Abramson, who makes clear here and elsewhere that he is no supporter of current attempts to mandate vaccination. Abramson is also featured in this essay by Arthur Allen, "Why It's Too Soon for a Mandatory HPV Vaccine," published in the New Republic Online.

• Also mentioned in the Washington Post story above is the imminent action by Virginia Gov. Tim Kaine to sign legislation making his state the second to mandate HPV vaccination. The requirement would not take effect until 2008 or 2009 and would include the traditional types of exemptions (increasingly referred to in the media, accurately, as an 'opt-out provision'.) More information can be found in this story.
  

New data on HPV prevalence; conflicting thoughts on relevance to vaccine debate

Last week's JAMA paper by Dunne, et al., -- "Prevalence of HPV Infection Among Females in the United States" -- garnered a significant bit of media attention. An accompanying editorial, "Estimating the Population Prevalence of HPV," by Weller and Stanberry, makes a point of examining the implications of this data to HPV vaccination policy, specifically cost-effectiveness calculations. (Free abstracts; subscription required for full text).

Here's some of the coverage of the paper by the popular press: Associated Press, Dallas Morning News, Washington Times, and Washington Post.

The data has provided ammunition for both sides of the vaccine mandate debate. Proponents of vaccination (and mandates, specifically) are pointing to the surprisingly high prevalence of HPV, of all types, in women: 24.8%

Those on the other side note the study's findings that the specific HPV types included in Gardasil are present in only 3.4% of females. To critics of mandates, this suggests that it is unnecessary to vaccinate all young girls when only a small percentage of females have the specific strains included in the vaccine. However, these numbers do not change the overall facts regarding cervical cancer incidence and mortality.

If anything, the ways in which the Dunne, et al., paper's findings have been used and will continue to be used in the Gardasil debate offer a valuable lesson of the potential dangers of using statistics in isolation to advance a policy argument.

More on Texas HPV vaccine mandate backlash

There continues to be a tremendous amount of coverage of Gardasil in the media, most of it focused on reaction to Texas Gov. Rick Perry's nearly-three-week-old executive order rather than the vaccine itself, HPV, or cervical cancer.

Saturday's New York Times wrote about the "Furor on Rush to Require Cervical Cancer Vaccine." The story's premise:

"But a roaring backlash has some health experts worried that the proponents, including the vaccine's maker, Merck, have pushed too far too fast, potentially undermining eventual prospects for the broadest possible immunization."

Syndicated columnist Clarence Page writes, "Don't judge cancer vaccine by Austin political fallout," attempting to encourage the public to distinguish the political controversy created by Perry's actions from the merits and potential benefits of the vaccine itself. He argues,

"With emotions heated up, a lot of misinformation and unnecessary anxieties already are being stirred up over the new vaccine. The least grounded appears to be the fear that it will encourage more sexual activity outside marriage. Our society unfortunately has many larger reasons for that and it is a worthy debate for another time.

For now, Gardasil appears to be a very important and welcome life-saving step forward in the fight against cancer. Don't judge it by the political confusion it has caused."

For an example of emotions heated up, take a glance at this political cartoon at Newstarget.com.

A few more op-eds of note: In Newsday, Marc Siegel writes in favor of broad vaccination (though not explicitly addressing the question of mandates). In the Atlanta Journal-Constitution, Former Rep. Bob Barr writes against mandates, in part:

"None of these concerns will likely deter the legion of Big Government types out there who — allied with the many do-gooders populating state legislatures from California to New York, and prodded by companies willing to spend millions to make billions — will allow nothing to stand in the way of 'good government,' whether the people want it or not."

As far as news goes, the latest in Texas is an effort in the state legislature to effectively reverse Perry's executive order. According to this story, a hearing on the topic yesterday went well into the night. The Houston Chronicle has more.

Finally, the Arts and Leisure section of Sunday's New York Times took a closer look at the visual and creative elements of Merck's "One Less" television commercial.

Voices on HPV vaccination, Texas mandate

Of the many opinions expressed in the media over the past 10 days regarding the executive order by Texas Gov. Rick Perry, here are a few worth noting:

• Friday's USA Today included a point-counterpoint on the Texas mandate order. The USA Today editorial board questions the timing of the mandate. The headline and subhead of the story sums up their argument nicely: "Rush to require cancer shot threatens to promote backlash; HPV vaccine holds great promise, but Texas mandate is premature."

• On the same page, Gov. Perry (or more likely, a member of his staff) responded in a short commentary titled "My order protects life." It frames the decision less as a matter of instituting a 'mandate', but rather, implementing an 'opt-out' system of vaccination instead of an 'opt-in' system. Given the relative ease of obtaining exemptions (to the chagrin of vaccine advocates), that terminology is probably more precise than speaking about 'mandates', with its connotation of compulsion.

• Arthur Allen, author of Vaccine (which we noted previously and was reviewed this weekend in the Washington Post) wrote an op-ed that appeared in several papers last week. Titled "Idea behind the decision is sound, but Perry's timing is off," the piece makes an argument similar to that of the USA Today editorial. He writes, "By imposing the HPV vaccine in such a rushed, questionable way, Mr. Perry's action threatens to mobilize people who, under normal circumstances, would simply do what they were told, assuming it was best for them."

• In this AP story in the Seattle Post-Intelligencer, Washington Gov. Chris Gregoire voiced skepticism at Perry's decision. "'I told the medical association that I was reticent to dictate when I think there is a lot of public education that needs to go on,' Gregoire said. 'To go out and start just saying everybody mandatorily has to have this is a little bit troublesome for me.'"

• Finally, Art Caplan and James Colgrove appeared on "Radio Times," a Philadelphia-based NPR program, to discuss HPV vaccination, the Texas mandate, and related topics regarding the ethics of vaccines. You can listen to the one-hour program here.

Texas HPV vaccine mandate in the news

There has been a great deal in the news this week about Gardasil (and a corresponding spike in our traffic), much of which has been triggered by Texas Gov. Rick Perry's executive order on Friday requiring sixth-grade girls to be vaccinated against HPV. Here's the text of the executive order and an accompanying press release from the governor's office. Quoting Perry, "Requiring young girls to get vaccinated before they come into contact with HPV is responsible health and fiscal policy that has the potential to significantly reduce cases of cervical cancer and mitigate future medical costs."

Perry, a Republican, has received criticism for this decision from members of his own political party and conservative organizations, as this AP story and this Houston Chronicle story explain. Perry released a second statement over the weekend, saying, in part,

"Providing the HPV vaccine doesn’t promote sexual promiscuity anymore than providing the Hepatitis B vaccine promotes drug use. If the medical community developed a vaccine for lung cancer, would the same critics oppose it claiming it would encourage smoking?

"Finally, parents need to know that they have the final decision about whether or not their daughter is vaccinated. I am a strong believer in protecting parental rights, which is why this executive order allows them to opt out."

Indeed, likely lost in the headlines pointing to a "mandate" is the important point that the exemption policies already in place in Texas will apply to HPV vaccination in the same way, including parents having the ability to decline vaccination for 'philosophical reasons'. In fact, proponents of vaccine mandates will likely be disappointed to learn that the executive order also instructs state officials to make the exemption process easier by creating a system in which parents can decline vaccination online.

Today's New York Times includes an editorial praising Perry for the decision. In fairness, it argues far more convincingly for HPV vaccination generally than it does for a state mandate (though strong arguments can certainly be made for it.)

Independent of discussions about the appropriateness of philosophical exemptions from vaccination (such as Paul Offit's op-ed we noted here), the current state mandate system means that no parents will be forced to vaccinate their children against their will. However, years of experience have shown that state mandates provide the structures and encouragement necessary to maximize a vaccine's benefit across communities, particularly reaching those without regular access to medical care whom cervical cancer targets disproportionately.

When considering vaccine mandates, we should not focus our attention on those with strong beliefs opposing vaccination, as the exemption procedures provide, for better or worse, a relatively simple remedy. Instead, we must consider those silent in these debates, those not receiving even basic medical care, much less tracking the minute-by-minute developments regarding Gardasil. For them, state mandates have been shown repeatedly to provide the awareness and stimulus needed for the vaccine to reach all who could benefit from it.

Updates on HPV vaccination outside the U.S.

Those looking for information on the policy discussions and implementation of Gardasil worldwide will be very interested in the latest issue of HPV Today, an international newsletter on all things related to HPV research, policy, and practice.

Among the items in the issue: a short piece by Dr. Luisa Lina Villa, a Brazilian cancer researcher, updating the international regulatory landscape for Gardasil. She notes that more than 40 bodies around the world have approved the vaccine thus far. Australia, New Zealand, Peru, and Mexico are among the few to approve the vaccine for males as well as females. Dr. Villa also describes some of the implementation challenges faced by her native Brazil, among them cost and the absence of an adolescent vaccination infrastructure.

Also in the issue: a very helpful table outlining the different approvals (by age, gender, condition, etc.) that Gardasil has received by various regulatory bodies around the world and a brief report on the results of a survey in Australia exploring whether the vaccine could promote unprotected sex among Australian teens. (The short answer: no)

GSK planning head-to-head comparison of HPV vaccines

Earlier this month, GSK announced its plans to conduct a head-to-head clinical trial comparing its HPV vaccine, the still-unlicensed Cervarix, with Merck's Gardasil. Here's the GSK press release and a provocatively-headlined story from the Philadelphia Inquirer, "Area drug firms go to war over vaccine."

As the story notes, such a trial design is rare in medicine and all but unheard of for a vaccine. There's little doubt that this move by GSK is an attempt to frame an argument for the superiority of its HPV vaccine, despite the numerous advantages of Merck's Gardasil at present, among them, an increasingly longer head start in the market, immense media coverage over the past year, data showing 100% effectiveness (with respect to the HPV strains included in the vaccine), and the additional protection it provides against genital warts. Whatever their motives, head-to-head comparisons are helpful to patients and physicians, and it would by no means be a bad thing for other manufacturers of pharmaceuticals and vaccines alike to follow this lead, despite the high risks.

A sidebar piece in the same issue of the Inquirer looked at cost and access issues related to Gardasil. One interesting item: According to Merck's Richard Haupt, about $80 million worth of Gardasil had been sold through October, which he describes as "an extraordinary uptake." At Merck's listed price of $120/dose, that works out to roughly 660,000 doses, or enough to fully vaccinate 220,000 girls and women. (That number is likely higher, given the discounts offered to government programs and other groups).

More states introduce HPV mandate bills

A "wave of support" is how today's Washington Post describes the growing number of states in which bills to mandate HPV vaccination have been introduced in recent weeks. This story notes developments in Maryland, Virginia, and the District of Columbia, with many comments from politicians and physicians supporting the actions but nary a quote from opponents of the bills.

On Wednesday, a Washington Post columnist offered a very critical take on the D.C. measure and his views of the assumptions underlying the need for such a law in the city. Also of note is this counterpoint to the Post columnist's views in today's Washington Times, strongly supporting the proposed mandate.

Elsewhere, this story in Wednesday's Houston Chronicle discusses the debate likely to occur now that similar bills have been filed in both of Texas' state houses.

We're not generally in the business of forecasting the future, but it seems very likely that this momentum will lead to the passage of HPV vaccination mandates in at least some states in 2007. The fact that the exemptions (for medical, religious, and philosophical reasons) already available for other vaccine mandates are all but certain to apply to HPV requirements will likely play a significant role in how politicians react to the concerns of opponents of these bills. As a result, policy discussions of HPV mandates will be able to avoid entirely the difficult ethical questions raised by the exemption policies themselves, or, for that matter, the overall principle of mandating vaccination.

Michigan HPV mandate bill fails; similar bill introduced in Kentucky

This story from the Grand Rapids Press reports on the rejection of the bill in the Michigan legislature that would have mandated HPV vaccination for sixth-grade girls (while keeping the exemption system common to other vaccines). The bill, which passed the Michigan senate in September, was rejected by the state house during its last day in session prior to the holidays. The story above notes the intentions of two legislators to reintroduce the bill during the new session that has just begun.

Similar efforts are underway in Kentucky, according to this story from Friday's Lexington Herald-Leader. A bill that would require vaccination of girls prior to entering middle school was introduced by Rep. Kathy Stein and currently is being evaluated by the house's Health and Welfare Committee.

Gardasil: Profile of Merck Vaccines president; feature on early HPV-cancer link proponent

Two items worth reading for those interested in background content related to Gardasil's development and arrival:

• "Making her mark at Merck" (Business Week, 8 January) -- A profile of Margaret McGlynn, the president of Merck Vaccines. An interesting item in the story: "Analysts are counting on McGlynn to drive much of Merck's growth: Some predict revenues from her division will triple by 2010, to $6 billion." While the business of vaccines is not our area of expertise, this is point underscores the period of explosive growth for vaccines that we're just entering, one in which ethical considerations will demand that much more attention.

• "Cancer quest: How ex-Penn scientist's hunch led to cervical vaccine" (Philadelphia Inquirer, 24 December) -- A very lengthy feature (two pages in the print edition) on
  Dr. Harald zur Hausen, described in the story as a very early proponent (i.e., the 1960s) of a link between HPV and cervical cancer (the credit for proving such a link has gone to others in the early 1980s). A very interesting, seemingly well researched piece.
  

From NEJM: Ethics and Politics of HPV Mandates

This week's New England Journal of Medicine includes a commentary titled "The Ethics and Politics of Compulsory HPV Vaccination" by James Colgrove, an Associate Research Scientist at Columbia's Center for the History and Ethics of Public Health.

Colgrove -- a contributor to our Ethics of Vaccines Project -- does an excellent job outlining the many competing considerations that will influence states' decisions regarding possible mandates of HPV vaccination as a condition of school or day-care attendance. While there is not much new in the essay (particularly for regular visitors to this site), Colgrove's essay is, by far, the best available synopsis of the topic in print to date. Thanks to the folks at NEJM, its full text is available for free.

One problem (perhaps the only one) with the essay is Colgrove's simplistic characterization of the perspectives of bioethicists on the topic, a description that comes perilously close to caricature. He writes:

"Bioethicists, who generally hold the values of patient autonomy and informed consent to be preeminent, tend to be skeptical about compulsory vaccination laws. Not surprisingly, some have expressed wariness about or opposition to mandating HPV vaccination."

Colgrove surely must be aware that any attempt to describe how "bioethicists tend" to think about a specific policy issue is about as useful as trying to capture in one sentence what "politicians tend to think" about Iraq or what "judges tend to believe" about civil liberties, as though a single, dominant position exists on these topics. In fact, many bioethicists, particularly those coming from a public health background, are quite comfortable with state vaccine mandates, including those for HPV vaccination.

As for the "some" bioethicists expressing wariness, Colgrove cites only two papers on ethical aspects of HPV vaccination, one of which is written by Pitt's Richard Zimmerman (a paper we previously discussed here). While Zimmerman has written frequently on ethical topics in journals of the vaccinology community, it is a stretch to identify him as a bioethicist, let alone as one of two who represent how the discipline as a whole tends to think about vaccine mandates.

These criticisms aside, Colgrove's essay is well worth reading for anyone thinking seriously about the appropriateness of HPV mandates.

Survey of physician attitudes on HPV vaccination in Pediatrics

The December 6 issue of the journal Pediatrics includes an interesting paper titled, "A National Survey of Pediatrician Knowledge and Attitudes Regarding Human Papillomavirus Vaccination." (Vol. 118 No. 6 December 2006, pp. 2280-2289 -- free abstract, subscription required for full text. The survey was conducted by researchers at the University of Colorado at Denver, Children's Hospital in Denver, and the CDC.

A national sample of 431 physicians was surveyed "to determine physician characteristics, knowledge, and attitudes associated with an intention to recommend human papillomavirus vaccination," quoting from the abstract. Among the reported results:

"46% of respondents would recommend vaccination for 10- to 12-year-old females, 77% for 13- to 15-year-old females, and 89% for 16- to 18-year-old females. Corresponding rates for males were 37%, 67%, and 82%, respectively. Whereas 60% of respondents thought that parents would be concerned that human papillomavirus vaccination may encourage risky sexual behaviors, 11% reported that they themselves had this concern."

The main issue complicating attempts to assess the value of this data is that the survey in question occurred between August and October of 2005, long before HPV vaccines entered the public spotlight (and likely well before many practicing pediatricians gave the vaccine serious thought). There's no way to know what impact the events of the last six months (particularly the significant public support that seems to exist in favor of vaccination) has had on physician attitudes. Still, the paper is a helpful contribution to vaccine implementation efforts.

Penn research on HPV and vaccination willingness

We're generally more than a bit reluctant to post things based solely on press releases, but here's a very interesting item coming out of our own university about attitudes regarding HPV vaccination. The press release, "Likelihood of HPV Vaccination Affected by How Information Is Presented, Penn Study Reveals," describes a study presented last week at the American Association for Cancer Research's 5th Annual International Conference on Frontiers in Cancer Prevention Research.

A sample of 635 Americans was randomly assigned to read one of three different paragraphs explaining the purpose of HPV vaccination. Subjects were then asked about their willingness to receive the vaccine. The content of the paragraphs and corresponding results:

"One paragraph addressed how the vaccine protects against cervical cancer, another how the vaccine protects against cervical cancer and sexually transmitted infection and the third how the vaccine protects against cervical cancer, sexually transmitted infection and how it may or may not lead to increased sexual promiscuity among those vaccinated.... When women in the survey read that the vaccine protects only against cervical cancer, 63 percent indicated that they were very likely or somewhat likely to get the vaccine compared to 43 percent of women who read that the vaccine protects against cervical cancer and a sexually transmitted infection."

The survey was conducted by the Center for Excellence in Cancer Communication Research at Penn's Annenberg School for Communication. Without a published paper to consult, it's all but impossible at the moment to assess the strengths and weaknesses of the survey design and the overall value of these findings. (For example, the third paragraph about sexual promiscuity seems very peculiar, as does the absence of data regarding that portion of the survey.)

If confirmed, however, these would be very interesting insights regarding attitudes about sexually transmitted infections among potential recipients of HPV vaccines. We'll update you if and when the study appears in print.

Merck launches Gardasil ad campaign

Merck today announced the launch of a national advertising campaign for Gardasil. Information on the campaign, dubbed "One Less" (as in 'one less life affected by cervical cancer'), appears in this press release. The TV ads are available for viewing on the Gardasil website.

As the press release notes, this campaign follows earlier (and continuing) HPV education efforts supported by Merck, "Tell Someone" and "Make the Connection". Back in May, we wrote about some of the questions being raised by the company's "Tell Someone" campaign here (our most widely visited post in our 8-month history), particularly the omission of any reference to the then-still-unlicensed Gardasil. (Mentioning the vaccine in an ad before it was licensed would have violated FDA guidelines, but the ads still raised eyebrows among some.)

Regardless, the "One Less" campaign is unabashedly promoting Gardasil, as is entirely appropriate for Merck to do. From all appearances, if this isn't the first major national ad campaign for a vaccine, it will certainly be the largest by far, likely to supplement ads in medical journals (the traditional domain of vaccine advertisements) with those on television and other popular media. Yet another sign that the world of vaccines has entered a new, very different, and very promising phase in its history.

Speaking of Merck, there's a notable story in today's Times of Trenton from Dow Jones Newswires -- "Merck stakes its future on demand for vaccines." In yet another story explaining the growing importance of vaccine sales to pharmaceutical companies, there are some interesting facts about Gardasil's production facilities and plans. For example...

"In a plant that Merck expanded a few years ago while Gardasil was still being tested in clinical trials, three shifts of employees now work around the clock producing the vaccine. So far, at least 750,000 doses have been shipped since Gardasil's June launch, contributing to sales of more than $80 million so far."

HPV: favorable data for male vaccination; VFC action; CDC shift in research focus

A paper published in the November issue of the journal Pediatrics includes new data from Merck on some of their ongoing trials of Gardasil in different populations. It's a highly technical paper with an equally complex title: "Comparison of the Immunogenicity and Reactogenicity of a Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents and Young Adult Women." (free abstract; subscription required for full-text).

To summarize, the paper reports the results of trials examining whether the vaccine's response in 10-15 year olds mirrors what's been shown in older females (16-23 year-olds). The short answer is that it does generate a comparable ('noninferior,' in scientific jargon) immune response in younger populations. Good news. The most interesting finding from the perspective of potential ethical issues is the comparison of data between 10-15 year old boys versus girls. Boys had a nearly identical response to the vaccine as their female counterparts did as well as a virtually identical safety profile between genders. As the paper's authors (all of whom are employees or consultants of Merck, critics might note, despite that being an obvious result of a Merck trial) note:

"Our findings in boys lend support for implementation of gender-neutral immunization using this vaccine for the purpose of preventing the widespread morbidity and mortality from anogenital cancer, as well as dysplastic cervical and external genital lesions, in the general population."

Speaking of Gardasil, news earlier this week that the vaccine has officially been added to the federal government's Vaccines for Children program, ensuring its availability to uninsured children age 18 or under. Here's a brief story from UPI.

One final related item: a story from Wednesday's Washington Post, "CDC Shifts Vaccine-Data Focus," reports on the decision to refocus intensive data-collection activities on immunization in 22 major cities on teenagers rather than young children. The move is a result of multiple new vaccines recommended for adolescents, including vaccines against HPV, meningococcus, and tetanus/diphtheria/pertussis (Tdap).

The Lancet calls for mandatory HPV vaccination

An editorial in the current issue of the The Lancet is making news. (Free registration required.) It says, in part:

"For effective and long-term eradication of HPV, all adolescents must be immunised. Data from the vaccine trials in boys are urgently needed; in the mean time, EU member states should lead by making the vaccinations mandatory for all girls aged 11-12."

Here's coverage of the editorial from Forbes.com, the BBC, and the Telegraph. The Lancet is a bit imprecise about the status of the Michigan bill that would mandate vaccination -- while it did pass the Michigan Senate last month, House consideration of the bill will not begin until after next month's election, and its passage is by no means assured.

The biggest question is what the editorial means, precisely, when referring to making vaccination mandatory in the E.U. The term implies some program of enforcement and consequences for those who refuse vaccination. (In the U.S., of course, that takes the form of being prohibited from school or day-care.) These mechanisms don't exist in the E.U.; their establishment would represent a major policy change and an equally large philosophical shift regarding European vaccination efforts.

Perspectives on HPV vaccination, Michigan mandate bill

Yesterday's Lexington Herald-Leader included a pair of items about HPV vaccines with comments from a host of vaccine experts (and not-quite-experts). One story, "Is Prevention Worth a Shot?," offers general advice to parents. The other is a sidebar, "Feedback about Michigan Law," with comments on the bill under consideration that would mandate vaccination for girls in sixth grade. I was asked by the Herald-Leader for comments on the ethical merits of such a mandate. From the story, here are my remarks:

"Ethically, electing to mandate a vaccine for children requires weighing the societywide benefits of vaccination versus the infringement, however minor, on the decision-making authority of parents. Among the factors that influence this ethical analysis are the risk of infection, the severity of disease without vaccination, and, very importantly, the likelihood that a vaccination program can succeed without state mandates. Unfortunately, history tells us that vaccines in the U.S. have great difficulty achieving high levels of support without the power of mandates.

"The points above are true for any vaccine, but the HPV vaccine has unique considerations that point in favor of a mandate. We know that groups with reduced access to medical care, and particularly regular Pap screenings, are more likely to develop cervical cancer than the general population. They are also more likely to die as a result of it than cervical cancer patients overall. Without a mandate, there remains a great risk that those not getting Pap screens or other care will similarly not be reached by HPV vaccination efforts. Without a mandate, we may miss exactly the same people who stand to benefit most from HPV vaccination. Ethically, this is of great concern.

"While a mandate is not a silver-bullet solution to these potential problems, it would signify the importance of HPV vaccination and very likely lead to novel strategies by local health departments and school districts to deliver the vaccine to all girls in the target age group. A mandate puts the vaccine in the best position to save the most lives, while still allowing parents with philosophical or religious objections to opt out by means of the generally straightforward exemption policies."

ACIP: June minutes and October agenda

The folks at the Immunization Action Coalition pointed out that the full minutes from the June 2006 meeting of the CDC Advisory Committee on Immunization Practices are now available here. The 96-page PDF is the next best thing to attending the meeting yourself, as it provides comprehensive coverage of everything that took place. In June, of course, the major news was the recommendation vote for Merck's HPV vaccine, Gardasil. For those interested in the data that informed the ACIP's recommendation, the report is invaluable.

Also on the ACIP website is a draft agenda for the group's next meeting, scheduled for October 25-26. The most notable item is a scheduled vote on a recommendation for Merck's shingles vaccine, Zostavax, for use in adults.

Michigan bill would mandate HPV vaccination

It was only a matter of time until a state legislator offered a bill mandating HPV vaccination as a condition of school or day-care entry, yet the news from Michigan this week was somewhat surprising only for how quickly the time came. Here's the AP story from CNN and an editorial supporting the bill in the Detroit Free Press.

Noteworthy is the statement from the Free Press that the bill in the Michigan Senate was co-sponsored by every female member of the body, across the political spectrum. We've written previously about HPV mandates, but now that a bill has been offered, what goes on in Michigan in the weeks and months ahead will be an important test case for the reception HPV mandates receive from legislators and the public across the country in the future.

News, research, and opinion on HPV vaccines

While the amount of information and discussion about HPV vaccines continues to surpass all other vaccine issues combined, we'll periodically put together a post noting some of what comes to us that's of value for those looking for further info...

• Vaccine supplement -- Late last month, the international journal Vaccine published a special issue devoted exclusively to HPV vaccines. The 264-page issue (Vol. 24, Supplement 3) is beyond impressive, including a who's who of vaccine researchers and policymakers exploring virtually every imaginable aspect of HPV science and policy. Included are papers on immunology, epidemiology, public health, developing countries issues, social/behavioral aspects of vaccination, and many more. Abstracts are free, but a subscription (or access through a library) is necessary to view the full text of any paper. The perfect launch point for anyone interested in examining the medical literature on HPV vaccines.

• HPV Today -- An international newsletter devoted to all aspects of HPV infection and treatment, vaccines have (understandably) received considerable attention in recent issues. The current edition includes an interview with Harvard's Sue Goldie on decision science and what it reveals about HPV vaccine policy options.

• "Benefits of new vaccine outweigh ethics concerns" -- That's the title of an op-ed by our colleague Anita Allen in her regular column, "The Moralist", in Sunday's Newark Star-Ledger. Allen, a contributor to the Ethics of Vaccines Project, writes,

"New immunization programs always raise legitimate ethical concerns, and the recently proposed cervical cancer vaccine programs are no different. But the particular ethical concerns raised by the HPV vaccine should not stand in the way of public acceptance. The potential health benefits of the vaccine are enormous."

HPV odds and ends

A few of the relevant items from the media that have crossed our desks this week...

• "How a vaccine search ended in triumph" (New York Times, 8/29) -- Tells the very interesting backstory of attempts throughout the 20th century (and even into the 19th) to understand the true cause of cervical cancer. Even after HPV was confirmed to be that cause, the road to a vaccine was by no means an easy one, including taking researchers to a convent in upstate New York, of all places. For any medical historian, this story is a book waiting to be written.

• "Parents want HPV shots, but can't find them" (MSNBC, from AP, 8/29) -- In many respects, this is a great sign -- reflecting early enthusiasm for the vaccine which may translate to significant vaccination rates long before mandates enter the discussion. That the vaccine is hard to find is no fault of Merck, it appears, but rather the result of the typical bureaucratic maneuvers that follow licensure and ACIP recommendations, including the publication of 'official' recommendations in MMWR, action required by third-party payers to cover the cost of the vaccine, and reluctance by doctors to stock it until the payment landscape becomes clearer.
  

How to explain HPV vaccination's purpose to teens?

Among the many questions regarding the implementation of Gardasil on a large scale is how the purpose of the vaccine should be explained to children as young as 9 years old (but mostly 11-12) receiving it...

• What level of detail regarding HPV, its sexual transmission, and cervical cancer is appropriate?
  
• Should the physician handle these discussions alone, should they be left to parents to deliver, or should a team effort be employed?
  
• Should parents be permitted to instruct the doctor to give an 'abridged' version of the vaccine's purpose and function vs. the 'full' version they might otherwise deliver?
  
• In general, it's obvious that a discussion of Gardasil with a nine or ten year old would be dramatically different than one with a 13 or 14-year old (with added individual differences even within a specific age group). However, there's no clear guide to help physicians (or the other health care providers who will administer HPV vaccinations) tailor their discussions of the vaccine to children of varying ages, particularly in cases where there isn't an established physician/patient relationship to provide guidance as to a child's maturity, etc.
• What if a parent and child/patient have different opinions regarding whether to vaccinate? Is there a place for child assent to vaccination in these circumstances (particularly among older teenagers)?
  

With all that in mind, an AP story posted this weekend considers some of these questions. Titled "HPV vaccine creates parental challenge," the story follows a 14-year old girl and her mother as they learn about HPV vaccination from the girl's doctor. It's a useful way to begin thinking about these issues less on the national policy level and more from the perspective of individual patients and families. (Thanks to Dom Sisti for the heads-up.)

Gardasil provisional ACIP recommendations posted

As shown by the series of announcements in the past six months regarding Merck's rotavirus vaccine, there's a pattern for how ACIP recommendations become official -- first a vote at one of the committee's thrice-annual meetings, then the online posting of recommendations on the ACIP website a few months later, and, finally, publication in MMWR a few months after that. Only then are the recommendations truly 'official', for what that's worth. In the case of RotaTeq, the ACIP vote came on February 21, provisional recommendations were posted in May, and final publication occurred on August 10 (as we noted here).

Using this timetable for comparison, all signs point to Merck's HPV vaccine, Gardasil, being on a faster track. Recall that the ACIP vote took place on June 29 (as we discussed then), but the provisional recommendations are already posted here at the ACIP website, where they've been available for over a week. The only real news from the document is that publication of the official version of the recommendations in MMWR is tentatively slated for November. (Thanks to the Immunization Action Coalition for the heads-up.)

ACOG issues HPV vaccine recommendations

The American College of Obstetricians and Gynecologists announced their recommendations to ob/gyns for HPV vaccination in women age 9 to 26. Not exactly a surprise that the group supports routine vaccination, but it's an important action, as ob/gyns see the vast majority of women in the 'catch-up' immunization group -- age 13 and above. Coupled with efforts by primary care providers, encouragement for vaccination by ob/gyns increases the likelihood of high vaccination rates overall among the large catch-up population. There's ample evidence that official recommendations from professional groups such as this do influence physician practices.

Here's the ACOG press release as well as excerpts from the full recommendations posted yesterday on the ACOG website. The full recommendations will be published in the September issue of Obstetrics and Gynecology.

June ACIP presentations available online

We neglected to mention that the slides from speakers at June's ACIP meeting were posted online in the last few weeks. For those looking for details, data, references, and scientific sophistication well beyond anything available in the media (for understandable reasons), these are great resources, particularly regarding Merck's HPV vaccine, the main item on the June agenda.

The files available include several presentations on Gardasil (safety and efficacy data from Merck, cost-effectiveness analyses, recommendation details, etc.), as well as the many other topics the committee considered, including a new recommendation for varicella vaccination, updates on influenza, mumps, rotavirus, avian flu, and much more.

Two cautionary views on Gardasil

With essentially the same points being made repeatedly in editorial and op-ed pages across the country, we suspect that we'll be linking to far fewer opinion pieces regarding Gardasil in the weeks ahead. (Exceptions will certainly be made for essays such as Alice Dreger's that offer a unique perspective.)

Since nearly every commentary we've seen has offered unabashed praise for HPV vaccines, it seems fair to call attention to two commentaries published in the last few days offering a slightly more cautionary take while still supporting the vaccine generally (it would be hard not to).

The first was written by Peter Sprigg of the Family Research Council and published in Saturday's Washington Post. Titled, "Pro-family, pro-vaccine--but keep it voluntary," the op-ed begins by citing the positive reception the vaccine has received from the FRC and other conservative organizations. However, Sprigg then outlines two concerns: the first notes the importance of accurate communication about what level of protection the vaccine does and does not provide. His point that claims of Gardasil's "100 percent effectiveness," while accurate in their intended context, can create confusion when used less precisely is on target. (Data suggest the vaccine is 100% effective against the 70% of cervical cancer-causing HPV strains it targets.) Sprigg's second concern touches about the FRC's oft-stated opposition to mandating HPV vaccination as a condition of school entry, a decision the group (and others) believe should be left to families.

A second essay with a very similar thesis appeared in today's New York Times, titled "A new vaccine for girls, but should it be compulsory?" by Roni Rabin. Rabin advocates continued vigilance regarding pap smears (as nearly everyone does), but questions the ACIP universal recommendation for HPV vaccination due to the continued decrease in cervical cancer incidence in the past 50 years. In her essay, she suggests the funds that will pay for the vaccine could be better spent on 'preventive health care' (a category that, for Rabin, apparently doesn't include vaccination). She also wonders aloud about as-yet-unknown potential safety concerns and the limited size of the clinical trial cohort of younger girls.

A first-person perspective on the potential impact of HPV vaccination

We've linked to a number of newspaper editorials on HPV vaccines over the past few months, nearly all in support of their broad availability. While those pieces were almost exclusively written in the traditional editorial page third person, this excellent op-ed in the Chicago Tribune earlier this month offers a powerful first-person look at the potential benefits of HPV vaccination.

Written by Alice Dreger, an Associate Professor of Medical Humanities and Bioethics at Northwestern University, the essay is titled "A shot that could save thousands of lives in the U.S." Despite the generic headline handed down by editors at the Tribune, Dreger's piece recounts her own experiences being infected with HPV strains known to cause cervical cancer and the impact of this on herself and her relationships, particularly with her husband. From this perspective, she offers a unique take on the ongoing discussions regarding which groups to vaccinate and potential opposition to its use in teenage girls.

Published earlier this month, the essay led to several letters to the editor that were printed Saturday, applauding Dreger for sharing her story and offering similar first-person experiences of HPV infection and its consequences.